Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation

Simple item page
dc.authoridTahir Turanli, Eda/0000-0002-0789-0398
dc.authoridEverest, Elif/0000-0001-7898-7800
dc.authoridTutuncu, Melih/0000-0002-9851-7002
dc.authoridSezerman, Osman Ugur/0000-0003-0905-6783
dc.authoridSiva, Aksel/0000-0002-8340-6641
dc.contributor.authorEverest, Elif
dc.contributor.authorAhangari, Mohammad
dc.contributor.authorUygunoglu, Ugur
dc.contributor.authorTutuncu, Melih
dc.contributor.authorBulbul, Alper
dc.contributor.authorSaip, Sabahattin
dc.contributor.authorDuman, Taskin
dc.date.accessioned2024-09-18T21:05:04Z
dc.date.available2024-09-18T21:05:04Z
dc.date.issued2022
dc.departmentHatay Mustafa Kemal Üniversitesien_US
dc.description.abstractMany multiple sclerosis (MS)-associated common risk variants as well as candidate low-frequency and rare variants have been identified; however, approximately half of MS heritability remains unexplained. We studied seven multiplex MS families, six of which with parental consanguinity, to identify genetic factors that increase MS risk. Candidate genomic regions were identified through linkage analysis and homozygosity mapping, and fully penetrant, rare, and low-frequency variants were detected by exome sequencing. Weighted sum score and polygenic risk score (PRS) analyses were conducted in MS families (24 affected, 17 unaffected), 23 sporadic MS cases, 63 individuals in 19 non-MS control families, and 1272 independent, ancestry-matched controls. We found that familial MS cases had a significantly higher common risk variation burden compared with population controls and control families. Sporadic MS cases tended to have a higher PRS compared with familial MS cases, suggesting the presence of a higher rare risk variation burden in the families. In line with this, score distributions among affected and unaffected family members within individual families showed that known susceptibility alleles can explain disease development in some high-risk multiplex families, while in others, additional genetic contributors increase MS risk.en_US
dc.description.sponsorshipIstanbul University-Cerrahpasa Scientific Research Projects [26360]; Istanbul Technical University Scientific Research Projects [41964]; Neurological Research Support Society-Turkey; Scientific and Technological Research Council of Turkey (TUBITAK) [ARDEB 1002, 220S889]; YUDAB program of the Council of Higher Education-Turkey; Intramural Research Program of NINDS, NIHen_US
dc.description.sponsorshipResearch grants for this study have been received from Istanbul University-Cerrahpasa Scientific Research Projects (No. 26360), Istanbul Technical University Scientific Research Projects (No. 41964), Neurological Research Support Society-Turkey, and the Scientific and Technological Research Council of Turkey (TUBITAK) ARDEB 1002 (No. 220S889). E.E. was supported by the YUDAB program of the Council of Higher Education-Turkey. D.S.R. is supported by the Intramural Research Program of NINDS, NIH. We thank Elaine F. Remmers for sharing their SNP data of Turkish control samples. We thank Clifton L. Dalgard and Uniformed Services University, Laboratory Core of the Collaborative Health Initiative Research Program, as well as Yale Center for Genome Analysis, for sequencing services. The authors gratefully acknowledge the support of Michael J. Lenardo both for his collaboration in exome sequencing of MS families and for his valuable comments and suggestions during our work.en_US
dc.identifier.doi10.1038/s41598-022-21484-x
dc.identifier.issn2045-2322
dc.identifier.issue1en_US
dc.identifier.pmid36216875en_US
dc.identifier.scopus2-s2.0-85139515328en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1038/s41598-022-21484-x
dc.identifier.urihttps://hdl.handle.net/20.500.12483/13340
dc.identifier.volume12en_US
dc.identifier.wosWOS:000865806900037en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherNature Portfolioen_US
dc.relation.ispartofScientific Reportsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAssociationen_US
dc.subjectScoreen_US
dc.titleInvestigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variationen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Tam Metin / Full Text
Size:
1.54 MB
Format:
Adobe Portable Document Format
Download

Collections

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu

We collect and process your personal information for the following purposes: Authentication, Preferences, Acknowledgement and Statistics.
To learn more, please read our privacy policy.

Customize